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Most of the preclinical studies based on animal models found that Nigella sativa extract in any form such N. sativa or the powdered form suggest its positive impact on the endocrine system. In particular, N. sativa appears helpful with regard to restoring the healthy histological architecture of endocrine tissue or its active constituents. In a general sense, it has manifested potential to directly remodel/modify their function, mitigating the hormonal disturbances seen in most common endocrine disorders such as thyroid dysfunction, metabolic, adrenal, and gonadal disorders. The therapeutic action of N. sativa is largely contributed by thymoquinone, a monoterpene compound. This monoterpene acts as a molecular scavenger of reactive oxygen species. It protects the endocrine tissue from the free radical species’ damaging effect and contributes in rebalancing hormonal disturbances. More extensive and rigorous preclinical research in combination with clinical studies can unravel the therapeutic properties and features of N. sativa in the context of specific endocrine disorders. At the same time working on technological novelties capable of improving its bioavailability and penetration potential is quite promising, while refining the regulatory framework of this research and its potential clinical implications is necessary.

Graves’ disease is an autoimmune disorder in which hyperthyroidism (over active thyroid) is caused by the autoantibodies against the TSH receptor. It is mainly characterized by the appearance of goiter. The symptoms are wide ranging as thyroid hormone affects many body systems. It is common in women and in people with age below than 40. Graves’ disease is caused by a combination of genetic and environmental factors while genetics being the main cause. Graves’ disease is not a single gene defect but has a complex pattern of inheritance. Today it is clear that genetic predisposition to Graves’ disease is caused by multiple genes. HLA gene is one the most studied gene predisposing to Graves’ disease. Lot of polymorphisms in this gene has been to be associated with the disease. Lymphoid tyrosine phosphatase encoded by the gene PTPN22 has been found to increase the risk of many autoimmune diseases including Graves’ disease. The best documented association of PTPN22 variants to autoimmune disorders including GD is rs2476601 (C1858T). Other genes associated with the risk of GD are thyrotropin receptor (TSHR), thyroglobulin gene, FCRL3, SCGB3A2, and CTLA4. This chapter will discuss in detail the genetics, pathophysiology, diagnosis and treatment of Graves’ hyperthyroidism.

AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by ARID1A-deficient cancer cells exhibited elevated PDL1 expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the ARID1A mutation and expression of ARID1A, TP53 and PDL1 genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of ARID1A gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the ARID1A, TP53 and PDL1 genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the ARID1A, TP53 and PDL1 gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of ARID1A and elevated mRNA expression of TP53 and PDL1 was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that ARAD1A under-expression and overexpression of TP53 and PDL1 might be crucial for tumor progression with TP53 and PDL1 acting synergistically.

Interleukin-17A (IL17A) is a proinflammatory cytokine and is assumed to play an important role in fetal rejection. In order to evaluate the potential role of IL17A polymorphism in the pathogenesis of recurrent miscarriage (RM), serum IL17A levels were estimated by ELISA. Single-nucleotide polymorphism was assessed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) using gene-specific primers and the EcoNI restriction enzyme. Serum IL17A levels were nonsignificantly (p > 0.5) low in RM patients compared with the control group. IL17A gene amplification by PCR yielded the undigested product of 815 bp, and its digestion with EcoNI enzyme produced 815, 529, 286, and 270 bp fragments for the GG genotype; 529, 286, and 270 bp fragments for the GA genotype; and 529 and 286 bp fragments for the AA genotype. The genotype frequency between the RM and control groups exhibited a significant difference (p = 0.001), whereas no significant difference was observed between allele frequencies in the two groups (p = 0.0954). These data suggest that the IL17A gene polymorphism exhibits no significant effect on IL17A gene expression. However, it significantly decreases and increases RM risk in the homozygous and recessive models, suggesting its potential pregnancy-protecting and -harming roles in the AA and GA + GG genotypes, respectively.

Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while. Keywords: Marine, Anti-cancer, Natural products, Corals, Marine herbs, Seaweeds

SARS-CoV-2 pandemic has greatly affected healthcare workers because of the high risk of getting infected. The present cross-sectional study measured SARS-CoV-2 antibody in healthcare workers of Kashmir, India.MethodsSerological testing to detect antibodies against nucleocapsid protein of SARS-CoV-2 was performed in 2003 healthcare workers who voluntarily participated in the study.ResultsWe report relatively high seropositivity of 26.8% (95% CI 24.8-28.8) for SARS-CoV-2in healthcare workers, nine months after the first case was detected in Kashmir. Most of the healthcare workers (71.7%) attributed infection to the workplace environment. Among healthcare workers who neither reported any prior symptom nor were they ever tested for infection by nasopharyngeal swab test, 25.5% were seropositive.ConclusionWe advocate interval testing by nasopharyngeal swab test of all healthcare workers regardless of symptoms to limit the transmission of infection within healthcare settings.

Objective: The objective of this study is to study association between testosterone and diabetes in Kashmiri males. Subjects and methods: A total of 300 males with Type 2 diabetes visited an outpatient and inpatient clinic at Shri Maharaja Hari Singh (SMHS) hospital, Srinagar, J&K India. The blood sugar and HbA1c, which are the markers of diabetes, and sérum testosterone levels were measured. The blood samples from both the cases and controls were collected. Results: Out of 300 subjects, 42% had a testosterone deficiency. A relationship between type 2 diabetic males and healthy males was observed, and testosterone levels were determined to be significantly lower among diabetic males (p < 0.001) when compared to healthy males. Then, we compared diabetic markers among testosterone deficient and normal testosterone level groups; the mean fasting plasma glucose (p = 0.0019) and glycated haemoglobin (HbA1c; p = 0.0449) levels were significantly higher in the testosterone deficient group than in the control group. To elucidate the relationship between the serum total testosterone level and fasting plasma glucose and HbA1c values, Pearson's correlation test was performed. Fasting plasma glucose levels (r = −0.252, p = 0.001) and HbA1c values (r = −0.697, p = 0.001) showed a significant negative correlation with serum testosterone levels among diabetic males. Conclusions: This study shows that diabetes causes low testosterone levels among males, and lower testosterone levels can act as a marker for diabetes. Thus, with timely intervention, mortality and co-morbidity associated with diabetes can be prevented.

286The human population is growing rapidly throughout the globe. To feed the growing population; there has been a rapid increase in intensive agricultural practices. As a result, the volume and types of agricultural waste biomass have gone up. The common traditional approach to manage agro-waste has been its release to the environment either with or without any treatment. Such practices increase the risk of environmental pollution and public health hazards. With the advancement of biotechnology, many new techniques for the management of agricultural wastes (AWs) have been developed, which had enabled one to reduce the toxic and hazardous effects of waste. These techniques convert the agro-waste into eco-friendly and value-added products having the potential of providing sustainable raw material for utilization of living organisms, including humans. Some of the potential applications of agricultural residues that had been exploited with the aid of biotechnology had been discussed in this review.

Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. A novel and exciting cancer research field has involved miRNA for the detection and suppression of cancer. However, the actual mechanism which is adopted by these miRNA is still unclear. miRNAs have been used as a cancer-associated biomarker in several studies, suggesting their altered expression in various cancers compared to the normal cells. The amount of expression of miRNA can also be used to determine the stage of the disease, aiding in early detection. In breast, pancreatic, and hepatocellular carcinoma, and gastric cancer, cancer cell proliferation and metastasis has been suppressed by miR-146a. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz. TNF-α, NF-κB and MEK-1/2, and JNK-1/2. Further research is required for understanding the molecular mechanisms of miR-146a in lung cancer. The potential role of miR-146a as a diagnostic marker of lung cancer must also be analyzed. This review summarizes the tumor-suppressing, anti-inflammatory, and antichemoresistive nature of miR-146a in lung cancer.

Purpose of Review Human race is currently facing the wrath of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly transmittable and pathogenic RNA virus, causing coronavirus disease 2019 (COVID-19), the worst ever global pandemic. Coronaviruses (CoVs) have emerged as a major public health concern. Urgent global response to COVID-19 outbreak has been to limit spread of SARS-CoV-2 via extensive monitoring and containment. Various treatment regimens have been adopted to manage COVID-19, with known drugs and drug combinations used to decrease the morbidity and mortality associated with COVID-19. Intensive research on various fronts including studying molecular and structural aspects of these viruses and unraveling the pathophysiology and mechanistic basis of COVID-19 aimed at developing effective prophylactic, therapeutic agents and vaccines has been carried out globally. Recent Findings No approved antiviral treatment except remdesivir exists for SARS-CoV-2 till date though novel drug targets have been identified. However, worldwide frantic and competitive vaccine development pharmaceutical race has borne fruit in the form of a number of promising candidate vaccines, out of which few have already received emergency use authorization by regulatory bodies in record time. Summary This review highlights the painstaking efforts of healthcare workers and scientific community to successfully address the COVID-19 pandemic—though damage in the form of severe illness, loss of lives, and livelihood has left a serious mark. Focusing on extensive research on various therapeutic options and antiviral strategies including neutralizing antibodies, potential drugs, and drug targets, light has been shed on various diagnostic options and the amazing vaccine development process as well.

Pharmaco-genomics determines the individual genetic mechanism for drug response and has the ability to transform tailored medication into clinical practice. A huge number of individuals die every year from adverse drug response since each person reacts differently to similar drug. The science of pharmaco-genomics has emerged as a potential discipline in the development of drugs and clinical medicine during the last several decades. It has offered a hope of protection for the patients against lethal health complications that arise from the adverse drug responses. The new medication approaches utilizing the science of pharmaco-genomics reduce the patient exposure to less or non-effective drugs or drugs with adverse effects. Same drugs have been reported to induce specific reactions in each individual owing to different nucleotide sequences in genes that encode the essential biological molecules such as drug-metabolizing enzymes, drug transporters, and drug targets. Single nucleotide polymorphisms (SNPs) are very helpful in determining the susceptibility of individuals to different diseases and drug reaction. These polymorphisms are the most prevalent in the genome of humans and account for 90% of genetic variance amongst individuals. Pharmaco-genomics may help in understanding the strong effects of inherited single gene variations on drug mobilization and action. The detection and characterization of SNPs related with disease risk and adverse drug response (ADR) is essential before using them as genetic tools. The credibility of SNP application in the diagnosis of diseases and possible ADR has been increased by the completion of HapMap project but still there are some challenges associated with it. The present chapter attempted to present the general role and effect of SNPs on pharmaco-genomics as well as their utility in clinical practice.

Background: Seroprevalence surveys are useful in estimating past infections and provide an appraisal of the cumulative number of infections in a population. We designed a population-based survey in Kashmir to estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in the general population aged 18 years and above. Methods: The survey was conducted among 110 villages and urban wards across ten districts in Kashmir from 17 Oct 2020 to 04 Nov 2020. Serum samples were tested for the presence of SARS-CoV-2 specific IgG antibodies using the Abbott SARS-CoV-2 IgG assay. Seroprevalence estimates were adjusted for the sampling design and assay characteristics. Findings: Out of 6397 eligible individuals enumerated, 6315 (98.7%) agreed to participate. The final analysis was done on 6230 participants. Seroprevalence adjusted for the sampling design and assay characteristics was 36.7% (95% CI 34.3%-39.4%). Seroprevalence was higher among the older population. Only one-half of symptomatic individuals reported having been tested. One out of every ten seropositive individuals reported a history of COVID-19 like symptoms. We estimated an infection fatality rate of 342 deaths per million infections. Interpretation: During the first seven months of the COVID-19 epidemic in Kashmir valley, approximately 37% of individuals were infected. There is still a significant pool of susceptible people in Kashmir. The number of infections will continue to rise unless infection prevention measures are practiced by the population. Funding: National Health Mission Jammu & Kashmir Declaration of Interests: We declare no competing interests, financial or otherwise. Ethics Approval Statement: The study was approved by the Institutional Ethics Committee of Government Medical College Srinagar.

BACKGROUND: SARS-CoV-2 infection (COVID-19) poses a tremendous challenge to healthcare systems across the globe. Serologic testing for SARS-CoV-2 infection in healthcare workers (HCWs) may quantify the rate of clinically significant exposure in an institutional setting and identify those HCWs who are at greatest risk. METHODS: We conducted a survey and SARS-CoV-2 serologic testing among a convenience sample of HCWs from 79 non-COVID and 3 dedicated COVID hospitals in District Srinagar of Kashmir, India. In addition to testing for the presence of SARS-CoV-2–specific immunoglobulin G (IgG), we collected information on demographics, occupational group, influenza-like illness (ILI) symptoms, nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) testing status, history of close unprotected contacts, and quarantine/travel history. RESULTS: Of 7,346 eligible HCWs, 2,915 (39.7%) participated in the study. The overall prevalence of SARS-CoV-2–specific IgG antibodies was 2.5% (95% CI, 2.0%-3.1%), while HCWs who had ever worked at a dedicated COVID-19 hospital had a substantially lower seroprevalence of 0.6% (95% CI, 0.2%-1.9%). Higher seroprevalence rates were observed among HCWs who reported a recent ILI (12.2%), a positive RT-PCR (27.6%), a history of being put under quarantine (4.9%), and a history of close unprotected contact with a person with COVID-19 (4.4%). Healthcare workers who ever worked at a dedicated COVID-19 hospital had a lower multivariate-adjusted risk of seropositivity (odds ratio, 0.21; 95% CI, 0.06-0.66). CONCLUSIONS: Our investigation suggests that infection-control practices, including a compliance-maximizing buddy system, are valuable and effective in preventing infection within a high-risk clinical setting. Universal masking, mandatory testing of patients, and residential dormitories for HCWs at COVID-19–dedicated hospitals is an effective multifaceted approach to infection control. Moreover, given that many infections among HCWs are community-acquired, it is likely that the vigilant practices in these hospitals will have spillover effects, creating ingrained behaviors that will continue outside the hospital setting.

Background and objectiveSARS-CoV-2 infection poses tremendous challenge to the healthcare system of nations across the globe. Serological testing for SARS-CoV-2 infection in healthcare workers, which form a high-risk group, helps in identifying the burden of hidden infection in an institutional setting.MethodsWe present the results of a cross-sectional serosurvey in healthcare workers from two different hospital settings based on their role in the management of SARS-CoV-2 patients in District Srinagar, Kashmir. In addition to testing for the presence of SARS-CoV-2 specific IgG, we collected information on influenza-like symptoms in the last four weeks and the status of RT-PCR testing. SARS-CoV-2 specific IgG antibodies were detected in serum samples using a sensitive and specific chemiluminescent microparticle immunoassay technology.Interpretation and ConclusionOf 2915 healthcare workers who participated in the study, we analysed data from 2905 healthcare workers. The overall prevalence of SARS-CoV-2 specific IgG antibodies was 2.5% (95% CI 2.0-3.1) in the healthcare workers of District Srinagar. Healthcare workers who had ever worked at a dedicated-COVID hospital had a substantially lower seroprevalence of 0.6% (95% CI: 0.2 - 1.9). Among healthcare workers who had tested positive for RT-PCR, seroprevalence was 27.6% (95% CI: 14.0 - 47.2).The seroprevalence of SARS-CoV-2 infection in healthcare workers of District Srinagar is low, reflecting that a high proportion of healthcare workers are still susceptible to the infection. It is crucial to lay thrust on infection prevention and control activities and standard hygiene practices by the healthcare staff to protect them from acquiring infection within the healthcare setting.

Background Prevalence of IgG antibodies against SARS-CoV-2 infection provides essential information for deciding disease prevention and mitigation measures. We estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar. Methods 2906 persons >18 years of age selected from hospital visitors across District Srinagar participated in the study. We tested samples for the presence of SARS-CoV-2 specific IgG antibodies using a chemiluminescent microparticle immunoassay-based serologic test. Results Age- and gender-standardized seroprevalence was 3.6% (95% CI 2.9% to 4.3%). Age 30–69 years, a recent history of symptoms of an influenza-like-illness, and a history of being placed under quarantine were significantly related to higher odds of the presence of SARS-CoV-2 specific IgG antibodies. The estimated number of SARS-CoV-2 infections during the two weeks preceding the study, adjusted for test performance, was 32602 with an estimated (median) infection-to-known-case ratio of 46 (95% CI 36 to 57). Conclusions The seroprevalence of SARS-CoV-2 specific IgG antibodies is low in the District. A large proportion of the population is still susceptible to the infection. A sizeable number of infections remain undetected, and a substantial proportion of people with symptoms compatible with COVID-19 are not tested.

Human polycystic ovary syndrome (PCOS)—a cluster of diseases displays various symptoms associated with endocrine and gynecological disorders in childbearing women. Oral contraceptive pills (OCP) being a drug of choice minimizes symptoms and complications associated with the disorder. But, the controversial data available in literature regarding use of OCPs compels us to setup a study design regarding effect of OCP treatment in PCOS subjects and the possible outcomes specifically regarding coagulation pathways. Two PCOS study groups have been selected according to Rotterdam Criteria: one with OCP treatment (n = 50) and other without any drug treatment i.e., drug naive (n = 50). Anthropometry, Biochemistry, Hormones, Insulin and various clotting factors like Factor XI, Factor V, tPA, TAT-III and D-dimer were analyzed in both groups. The results showed worsening of IR, Metabolic parameters and coagulopathy in OCP group comparative to drug naive group indicating adverse effects of the OCP treatment which puts these women at risk for number of future clinical implications especially Cardiovascular and metabolic complications.

Background Diabetes, the current epidemic in the present world is the growing concern. Type 2 diabetes mellitus is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is characterized by genetic changes in various adipokine levels. Methods In this study, adult population ranging from (30–60 years) with sample size of 400 T2DM cases, 150 MetS cases and 300 controls, among which female: male ratio was 2.3. Samples were taken from the Department of endocrinology SMHS Srinagar. We estimated the correlation of various adipokine levels among T2DM subjects, and we observe association of SNP+276 and +45 polymorphism among T2DM and MetS cases with control groups. Adipokine levels were estimated by ELISA and polymorphism by RFLP-PCR, followed by sequencing. Results Our results suggested that adiponectin levels are found to be significantly lower in cases while as leptin and resistin levels were found to be higher in cases than normals. Leptin and resistin were found to be positively correlated whereas they were found to have significant negative correlation with adiponectin. The genotype and allele frequencies for SNP+45 did not differ significantly between the T2DM, MetS cases and control groups. For +276, the results revealed a trend towards an increased risk of T2DM for the SNP+276G allele as compared with the SNP+45T allele in the Kashmiri population. The genotype and allele frequencies of SNP +45 (T/G) in ADIPOQ were not significantly different between both T2DM and MetS cases and controls (P = 0.15 for genotype; P = 0.3 for allele). However, the genotype and allele frequencies of SNP +276 (G/T) of ADIPOQ was significantly found to be associated with the risk of developing diabetes and metabolic syndrome. Conclusion The present study revealed that the adiposity or its related complications involving type 2 diabetes mellitus, metabolic syndrome causes significant changes in adipokine levels, also there is a significant association between type 2 diabetes mellitus, metabolic syndrome and polymorphism in SNP+276 (G/T) of ADIPOQ gene which suggests its important role in type 2 diabetes mellitus and metabolic syndrome of Kashmir population.

Objectives Approx 1 billion people across various ethnic and age groups have vitamin D deficiency. The high prevalence of such a deficiency is an imperative public health issue because hypovitaminosis D is an autonomous risk factor for mortality in the general population. Beyond bone integrity and calcium homeostasis, it is involved in numerous physiologic and pathologic processes. The role of vitamin D in the pathogenesis and prevention of type 2 diabetes mellitus has sparked universal interest. Methods This hospital-based case-control study was designed to study the association between 25-hydroxy vitamin D (25[OH]D) levels and the vitamin D receptor (VDR) gene polymorphism with diabetes and to evaluate their roles as risk factors for diabetes. 100 cases and controls were taken. 25(OH)D levels were analyzed by the chemilumenescence method using a Siemens ADVIA Centaur analyzer. Genomic DNA was extracted and Taq-1 and Bsm-1 genotyping in the VDR gene was done by using the polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Results 25(OH)D levels of patients with diabetes were significantly lower than those of controls (19.26±0.95 ng/mL vs. 25.49±1.02 ng/mL; p=0.001). 25(OH)D levels were found to be inversely associated with glycated hemoglobin percentages in cases (r 2 =0.74). The results suggested that the single nucleotide polymorphisms Taq-1 t(T) allele and b (G allele) in Bsm-1 might be a susceptibility allele for diabetes in the Kashmiri population. Conclusions VDR gene polymorphisms appear to be an important genetic determinant in the progression of diabetes. Considering the important predisposition risk factor, we observed that Taq-1 and Bsm-1 were strongly associated with diabetes in northern Indians. But requires further study as a probable genetic risk marker for diabetes.

Molecular studies have implicated mutant B-type Raf kinase (BRAFMut) of MAP-kinase signalling pathway in the pathogenesis of several cancers including colorectal cancer. Recently, the prognostic and therapeutic relevance of the most frequent BRAFV600E mutation also has been highlighted in colorectal carcinomas (CRC). Thus, the aim of this study was to investigate the prevalence of BRAFV600E mutation and to determine the correlation between this mutation and indicators of poor prognosis and outcome in patients with CRCs from Kashmir, North India. Here, we developed a highly sensitive technique, mutation allele-specific multiplex PCR (MASMP), for detection of BRAFV600E/BRAFc.1799T>A mutation, the results of which were confirmed by sequencing the product and compared to direct DNA sequencing. In total, BRAFV600E mutation status was analyzed in 57 colorectal tumour samples and an equal number of adjacent normal tissues. A high frequency of BRAFV600E mutation 21% (12/57) was identified in tumour tissues by MASMP compared to only 5.2% by direct DNA sequencing. Statistical analysis indicated that compared to BRAF-negative colorectal tumours, patients with BRAFV600E colorectal tumours were more likely to be >50 years old (61%) (P < 0.03). These tumours were more likely to be of clinical tumour stages III and IV (63%) (P < 0.04) with lymph node metastasis (52%) (P < 0.02) and characterised by a high-grade histology (63%) (P < 0.04). Colorectal patients harbouring BRAFV600E mutation experience more relapse/recurrence (52%) (P < 0.02). We, therefore, conclude that BRAFV600E mutation can be used as an indicator of poor prognosis to predict the outcome for CRC patients from Kashmir. MASMP proved to be a simple, sensitive and reliable technique for screening patients for BRAFV600E mutation. Testing for this mutation may be useful for selecting initial therapy mode and for follow-up monitoring in CRC patients.

Cancer has been generally related to the possession of numerous mutations which interrupt important signaling pathways. Nevertheless, deregulated immunological signaling is considered as one of the key factors associated with the development and progression of cancer. The signaling pathways operate as modular network with different components interacting in a switch-like fashion with two proteins interplaying between each other leading to direct or indirect inhibition or stimulation of down-stream factors. Genetic, epigenetic, and transcriptomic alterations maintain the pathological conduit of different signaling pathways via affecting diverse mechanisms including cell destiny. At present, immunotherapy is one of the best therapies opted for cancer treatment. The cancer immunotherapy strategy includes harnessing the specificity and killing mechanisms of the immunological system to target and eradicate malignant cells. Targeted therapies utilizing several little molecules including Galunisertib, Astragaloside-IV, Melatonin, and Jervine capable of regulating key signaling pathways can effectively help in the management of different carcinomas.

Vitamin D receptor (VDR) mediates cellular processes like cell cycle arrest and apoptosis which effect cancer susceptibility. VDR single nucleotide polymorphisms (SNPs) have a significant influence on functioning of VDR protein and subsequently contribute to the risk of cancer occurrence and progression. The present case–control study was carried out between 2016 and 2020 to investigate the association of VDR BsmI/ApaITaqI SNPs with Gastric Cancer (GC) risk in ethnic Kashmiri population not only for establishing a molecular marker for GC but also to facilitate the outcomes of personalized medicine in future. The polymorphisms of BsmI and ApaI of the VDR gene were evaluated using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism followed by Di-Deoxy Sanger sequencing in 143 GC cases and 150 controls. The mean age (in years) was 53.5 ± 7.92 and 51.2 ± 8.25 and mean Body mass index was 22.68 ± 4.27 kg/m2 and 23.81 ± 3.71 kg/m2 for cases and controls respectively. The mean CEA levels of GC cases was 40.2 ± 10.9 ng/ml. Genotypic distribution of VDR BsmI differed significantly between GC cases and controls (GG vs GA + AA; adjusted P = 0.014) and followed dominant mode of inheritence. Stratification of VDR BsmI revealed that frequency of variant genotype (GA + AA) was significantly higher in Preobese GC cases (P = 0.001), GC patients consuming

Honey is a by-product of flower nectar formed by the enzymatic action within the digestive tract of honey bee (Genera Apis). Several compounds in honey are known to possess potent therapeutic properties against several diseases including inflammation, bacterial infections, cardiovascular problems, etc. This chapter specifically summarizes the therapeutic properties of honey for the treatment of rheumatoid arthritis, osteoporosis, and other related diseases. The compounds responsible for these properties and their mechanism of action is also discussed.

Metabolic disorders occur when unusual chemical reactions take place in the body amend usual metabolic pathways. Diabetes mellitus a metabolic disorder is generally characterized by high glucose level in blood over longer period of time. In type 1 diabetes, pancreas fails to produce adequate insulin and the same effect is due to the loss of beta cells of pancreas. Type 2 diabetes begins with resistance to insulin and accordingly gives no response to insulin. Gestational diabetes mellitus is similar to type 2 diabetes in various aspects and is having combination of inadequate insulin and sensitivity to it. For many years, honey is being used as a substitute for sugar and for providing medicinal benefits. In animal as well as human studies, convincing evidence specifies that honey displays antidiabetic as well as hypoglycemic effects. Additionally, honey consumption improved other disorders related to metabolism and to diabetes such as reduced levels of HbA1c (glycosylated hemoglobin) and hepatic transaminases and increased HDL cholesterol. The same was in addition to lowering hyperglycemia and oxidative stress. Besides depicting hypoglycemic effect, research has indicated that honey improves lipid anomalies in rats and humans suffering from diabetes. The beneficial effects of honey could also be limiting other disorders of metabolism and lessening damaging effects on various organs of the body that ultimately result in diabetic complications. Although there are few studies in the literature which are contrary to the above-depicted discussions regarding the beneficial effects of honey and its use in diabetic disorder. Also the clinical trials or studies on humans (both diabetic and healthy) are rather very sparse. It is anticipated that this book chapter will encourage fundamental investigation intended at explicating the mode of actions by which oligosaccharides present in honey improves antidiabetic/hypoglycemic effects.

Honey has been and is being used for medical, pharmaceutical, and domestic needs. Besides, it is used as a conventional medicine and has various pharmacological properties. A variety of polyphenolic compounds are stated in honey and among them important polyphenols are Caffeic acid (CA), Quercetin (QU), Chrysin (CR), Kaempferol (KF), Apigenin (AP), Galangin (GA), Acacetin (AC), Caffeic acid phenyl ester (CAPE), Pinocembrin (PC), and Pinobanksin (PB) that have evolved as potential pharmacokinetic agents in the cure of cancer. Caffeic acid, a naturally occurring phenolic compound commonly found in honey, is being comprehensively studied for its therapeutic use and is being described as a cancer-causing agent in preliminary studies, but the same compound in combination with other antioxidants has been revealed to repress colon tumors in rats. CAPE was similarly proposed to have anticarcinogenic, antimitogenic, immunomodulatory, and anti-inflammatory potential. In a related progressive study, influence of CA against UVB (280–320 nm) irradiation-induced IL10 appearance and stimulation of MAPKs (Mitogen-Activated Protein Kinases) in skin of mouse was observed. The findings strongly propose that chrysin exercises growth inhibitory properties either by prompting p38 MAPK leading to buildup of p21Waf1/Cip-1 protein or by arbitrating the repression of proteosome action. It is also a well-established fact that chrysin prompts cell death in association with stimulation of caspase-3 and Akt signal corridor, which plays a vital role in chrysin-incited cell death in U937 cells. Galangin and its antiproliferative outcome on HL-60 cells was expressed in a manner that is dependent on dose, and it also prompted DNA breakage without any loss of integrity of cell membrane. Similarly, quercetin was also shown in an in vitro study to impede HL-60 cell propagation in association with repression of cytosolic PKC (Protein Kinase C) and TPK (tyrosine protein kinase) membrane bound. Acacetin, another important flavonoid, was revealed to impede the propagation of A549 cells, prompt apoptosis, and block cell cycle promotion at G1 cell cycle phase and also heightened the appearance of p53 protein and Fas ligands. Besides was also depicted to impede HepG2 cell propagation and incite cell death by boosting p53 protein and Fas ligands as in case of A-549 cells. Kaempferol-mediated cell death in H-460 cells was complemented by substantial DNA coiling/condensation and amassing ATP content. Besides, it altered the levels of Caspase-3 and AIF (Apoptosis-Inducing Factor). Pinocembrin has been shown to induce loss of MMP (mitochondrial membrane potential) with further release of cytochrome c and processing of caspase 3 and 9 in colon HCT116 cancer cells. Apigenin has been shown to exert antiproliferative influence against colon, breast, neuroblastoma, cervical, and liver cancer cell lines. The chapter has clearly put forth certain honey-based compounds that have been tested in laboratory setups and have been revealed to be hopeful pharmacological agent for hindering cancer propagation.

Honey has been broadly recognized as a source of nourishment and medication by both old and new generations. It has been utilized by people to treat numerous illnesses through topical application for at least 2700 years, but recent researches have revealed the antiseptic and antimicrobial activities of honey. It has been seen as a powerful agent that can be used in various human pathologies. Different clinical examinations have affirmed that the use of honey to cutaneous injuries which are severely infected removes contamination from the injury and enhances tissue healing. Honey has been perceived as a successful antioxidant and antimicrobial agent for centuries. Utilized mainly for treating burns and surface wounds, it has thus been developed into clinical medicine, as medical grade honey. In spite of this, the underlying interest in the utilization of honey for antimicrobial treatment was significantly reduced, as antibiotics were discovered and used. Nonetheless, due to the alarming increment in the occurrence of organisms with antimicrobial resistance, specifically the expansion in multidrug resistance (MDR), the quantity of efficient antibiotics is decreasing at a larger rate than new medications are created. This serious situation has made numerous scientists to think back to the pre-antibiotic period for creating solutions, directing their consideration towards the mechanisms of action of antimicrobial activity of honey.

Honey comes with a legendary history of being used as an indigenous medicine to cure a number of diseases. Honey is an essential source of phenolic molecules such as flavonoids and phenolic acids. The most abundant flavonoids present in honey include flavones, flavanones, and flavonols. Flavonoids show diverse activities such as non-inflammatory, antiallergenic, antiviral, antimalignant, antimicrobial, however, the antioxidant activity has been studied widely. Honey also possess a diverse molecules of phenolic acids including p-coumaric, ferulic, caffeic acid, acetophenones, phenylacetic acids, syringic, vanillic, gallic acid, and so on which endow it with the therapeutic activities against pathogens, inflammation while at the same time shows antioxidant and healing properties. The phenolic compounds owing to their medical properties make honey a very critical and attractive prophylactic entity for the prevention of chronic diseases associated with oxidative stress including cancer, cardiovascular disease, diabetes, respiratory disease, hypertension, neurodegenerative diseases etc. In this chapter, a discussion has been made on classification, structure, and medicinal and health benefits of phenolic compounds.

Honey is a sweet viscous liquid produced by several species of honey bees (Genus Apis). These insects mainly feed on the floral nectar and by enzymatic activity and evaporation of water produce honey from this nectar by regurgitation. Honey has several varieties and is regarded as the superfood with several pharmaceutical properties. This chapter gives a detailed outline about composition, classification, and pharmaceutical and other applications of honey.

Bio-pesticides, envelops a wide range of entomopathogenic microbial pesticides, plant secondary metabolites and other important sources which have potential to replace synthetic pesticides. The improvements in microbial vermin control incorporate the usage of bacteria, fungi, protozoa, and nematode species that may aggressively repress the development of pathogenic and toxigenic miniaturized scale life forms on significant horticultural wares. Bio-pesticide items are currently accessible economically for the control of vermin and maladies. The main focus of bio-pesticide research is to make these bio-pesticide products accessible at farm level at a reasonable cost. The utilization of microbes and their quality items acquaints extra contemplations with the toxicological portion reaction relationship, including a need to decide the credibility of irresistible and immunological impacts in relationship with human introduction to these bio-pesticides in nourishment or the environment. Investigations of significant equality propose that nourishments at present got from plant fused protectants are not prone to contrast from regular sustenance. Notwithstanding, there is general agreement that the logical strategies to survey dangers from hereditarily changed sustenance and smaller scale creatures will keep on advancing later on. Besides, bio-pesticide research is as yet going on and further research is required in numerous angles including bio-formulation and zones, for example, commercialization. This chapter has reviewed the significant and fundamental deserting of major bio-pesticides before. The future prospects for the improvement of new bio-pesticides are likewise discussed.

Changes in life style, urbanization, intensive agricultural practices and population explosion have led to an enhanced build-up of organic wastes in the environment. These organic wastes can contribute negative impacts on the environment. The nutrient recovery from organic wastes such as kitchen waste, agricultural waste and municipal waste is an essential part of their management and for decreasing degradation of the environment. Vermicomposting technology is a promising tool for recycling/management of organic waste and is socially acceptable, economically viable and environmentally sustainable technology throughout the world. Through this process organic waste is broken down by different species of earthworms, and a fine humus-like material known as vermicompost is produced. The produced vermicompost is very rich in both micro- and macronutrients like Ca, Mg, Zn, B, P, K, N, etc., useful soil microorganisms (nitrogen-fixing bacteria and phosphate-solubilizing bacteria) and plant growth promoters and hormones such as auxins, gibberellins and cytokinins and therefore can be used as an organic fertilizer for proper growth of plants. It can also be used as a replacement to harmful inorganic fertilizers. Therefore, vermicomposting technology is like killing two birds with one stone as organic waste is managed properly and at the same time organic fertilizer is produced.

Honey is a naturally occurring sweet substance with gummy consistency produced by honey bees. It is also formed by nectar-producing plants and trees. Honey is well known for its usefulness which is mainly attributed to its flavonoid components. Cardiovascular diseases are the single largest cause of early mortality, especially in developed countries but are also emerging in developing countries at an alarming rate. In most of the cases, atherosclerosis has remained as its main underlying pathological cause. The basic pathology behind atherosclerosis is due to a chronic inflammatory process in the endothelium of arteries. Oxidation of the neo-intimal lipids that releases oxidized molecular species eventually leads to vascular atherosclerotic changes. Formation of reactive oxygen species (ROS) in excess amounts due to oxidation of DNA, proteins, carbohydrates, lipids and other bio molecules adds on to these vascular changes. Antioxidant defence mechanisms of our body fail to balance this surplus ROS production, hence producing oxidative stress. Oxidative stress is associated with various metabolic disorders like cardiovascular diseases, systemic hypertension, diabetes mellitus, etc. Honey plays a protective role in a number of metabolic disorders as well as in cardiovascular health mainly due to its rich flavonoid and antioxidant content. Honey is believed to decrease the risk of developing elevated blood pressure. Intake of honey has the capability to decrease systolic blood pressure in healthy subjects. Honey also balances the lipid profile by increasing high-density lipoprotein (HDL) levels and reducing the levels of triglycerides and very low-density lipoproteins (VLDL). In this chapter, we have discussed how honey intake can help in prevention of cardiovascular disorders that has significant mortality and morbidity. A balance between the antioxidant intake and free radical injuries can help our body’s defence mechanism to overcome different forms of oxidative stress. Honey may prove as a useful substance that can help in the improvement of biochemical imbalances in the human body.

Honey and propolis are the honey bee-derived products with a long history of consumption by humans for health purposes. Both of these substances consist of a wide spectrum of vital compounds especially phenolics and flavonoids that are capable of exerting beneficial clinical effects on health. The antimicrobial, anti-metastatic, anticancer, anti-inflammatory, antioxidant, and anti-proliferative activities of honey ingredients and antiviral, antifungal, antimicrobial, anesthetic, anti-inflammatory, antioxidant, anti-protozoal, anticancer, antihepatotoxic, antihypertensive, and cytotoxic properties of propolis make these substances potential candidates for therapeutics. Honey has been found effective in the treatment of diabetes mellitus, cardiovascular disorders, respiratory ailments, neurological abnormalities, gastrointestinal defects, skin ulcerations, ophthalmic defects, wounds, peptic ulcers, and different types of carcinomas. Likewise, propolis also exhibits potential role in the management of chronic kidney disease, neurological disorders, tumors, ulcers, chronic periodontitis, atherosclerosis, gastrointestinal defects, and wounds. Evidences suggest honey and propolis as potential phyto-derived clinico-pharmacological agents for effective treatment of different diseases.

Honey—an important natural compound and a renowned native food product—is exploited since immemorial times for its medical properties. Its medicinal properties have fascinated the humans so much as it has earned a dominating spot in conventional medicine. Currently more research is going on in exploring the natural compounds present in the honey for promoting human health. Honey contains more than 200 bioactive components besides glucose, fructose, minerals, vitamins, amino acids and enzymes (Da Silva et al., Food Chem 196:309–323, 2016). The composition of honey depends on the type of plants on which honeybee (Apis mellifera) nourishes. Different kinds of phytochemicals present in the honey with high phenolic content, polyphenols and flavonoids mainly contribute to its high medicinal properties including its antioxidant and anticancer action (Iurlina et al., Food Chem 115:1141–1149, 2009; Pyrzynska and Biesaga, TrAC Trends Anal Chem 28:893–902, 2009; Yao et al., Food Chem 81:159–168, 2003). The polyphenolic compounds present in the honey have been found to possesses anti-proliferative effects against various types of cancers (Jaganathan and Mahitosh, J Biomed Biotechnol 2009:830616, 2009). These studies summarized the significant role of the bioactive species present in honey for different diseases. In this review, we critically examine the anticancer properties and molecular mechanisms of different bioactive components present in honey.

Pesticides are the chemical compounds with toxic nature employed to destroy a range of harmful organisms. A number of pesticides have been utilized during the past decades with the purpose of protecting the crops from pests. Even if these pesticides tremendously increase the crop yield, simultaneously they pose grave threat to the stability of the ecosystem. Pesticides threaten the long-lasting survival of key bionetworks, disarray the ecological relationships among living beings, and cause the loss of biological diversity. The survival of terrestrial, aerial, and aquatic organisms including human beings has been endangered by pesticides. The freshwater bodies are particularly at the risk of pesticide pollution due to the penetration of pesticide into them via run off, drifting, leaching, and drainage. The excessive use of noxious pesticides, for example, carbamates and organophosphates, has degraded the environment and threatened the existence of nontarget life forms including fish fauna via affecting their cholinergic systems. Pesticides deteriorate the health of fish by impairing their metabolic process that occasionally causes death of fish. The excessive consumption of pesticides has augmented the global apprehensions for the management of secure and sustainable environment. Ecological stability may be well conserved by replacing pesticides with the application of substitute techniques that include biocontrol, integrated pest management, genetic control, physical interventions, and sterile insect technique as well as the use of selected pesticides. Further research is required to produce eco-friendly species-specific pesticides so that the damage to nontarget organisms is avoided. This chapter talks about pesticides, their historical background, classification, pesticide toxicity in fish, and routes of pesticides exposure to fish. This chapter also discusses about the effects and threats posed by pesticides to fish life as well as challenges in monitoring pesticides. At the end of this chapter, the remedial techniques that may replace the pesticides have been discussed.

Honeybees depend upon plants for everything they want to maintain the colony running; nectar and pollen that is their only carbohydrate and protein essential nutrients. In order to achieve their necessary nutritional requirement, honey bees eventually collect essential plant metabolites when component of nectar and pollen. In addition, several molecules exhibit biological activity which may become significant in the battle against pests and pathogens in the hive. Flavonoids, terpenoids, and polyphenols are essential biologically active ingredients found in honey and also have antioxidant properties. Nonetheless, for reasons of room, it is practically impossible to give a detailed overview of the phytochemical characteristics of honey and pollen in a literature review of this scope. In addition, the therapeutic ability of biologically active ingredients and their use in value-added food products are also at the core of this chapter.

Honey is the material made by mixing of nectar and sweet deposits from plants and later on modified by honey bees. Honey is one of the most appreciated and valued natural products introduced to humankind since ancient times. Honey is a nutritional material that is traditionally known for its medicinal properties. Honey is used as a traditional medicine in treating various clinical ailments from wound healing to cancer apart from being used as a nutritional product. In dermatology, honey is used in the treatment of eczema, ulcers, wounds, atopic dermatitis (AD), allergies, and much more due to its antioxidant, antimicrobial, anti-inflammatory properties. In conclusion, honey could be considered as a natural therapeutic agent for various medicinal purposes. Sufficient evidences recommend the use of honey in the management of disease conditions especially skin- related disorders. Based on these facts, the use of honey in clinical wards is highly recommended. However, more rigorous scientific studies are needed to confirm its benefits in health care settings especially in the field of dermatology.